Lowering Blood Sugar to Decrease Inflammation Studied

< Sep. 16, 2009 > -- Using certain glucose-lowering medications in people newly diagnosed with type 2 diabetes does not appear to decrease inflammation associated with the development of heart disease, according to a new study.

The study looked at the use of metformin and insulin to lower blood glucose (sugar).

Even though these medications helped reduce glucose levels, the researchers found they did not affect inflammatory markers any more than a placebo medication did, according to a study published this week in the Journal of the American Medical Association (JAMA).

Diabetes is a metabolic disorder characterized by a failure to secrete enough insulin, or, in some cases, the cells do not respond appropriately to the insulin that is produced. Because insulin is needed by the body to convert glucose into energy, these failures result in abnormally high levels of glucose accumulating in the blood.

Diabetes may be a result of other conditions such as genetic syndromes, chemicals, drugs, malnutrition, infections, viruses, or other illnesses.

Diabetes Associated with Heart Disease

"Heart disease is one of the many co-morbidities associated with diabetes," explains study author Dr. Aruna Pradhan, an assistant professor at the Harvard Medical School and Brigham and Women's Hospital in Boston, and a cardiologist at the VA Boston Medical Center. "We thought by lowering glucose levels that we would also address inflammation. But, we found that going lower in glucose levels doesn't impact inflammation, which is a risk factor for heart disease."

This study follows other recent studies on diabetes and cardiovascular disease. Some suggested that intensive glucose control could not affect heart disease risk, while a recent meta-analysis suggests that good blood sugar levels could reduce death from heart attack, according to background information in Dr. Pradhan's study.

Almost 24 million Americans have diabetes, mostly type 2 diabetes, according to the American Diabetes Association. Risk factors for developing the disease include being overweight and being over 40, though younger and thinner people can also develop the disease.

Type 2 Diabetes Studied

Study participants included 500 men and women with type 2 diabetes diagnosed two years earlier on average. Slightly more women than men were included, and most of the study volunteers had a body-mass index above 30, which is considered obese. The majority of the study participants were white, and about one-quarter of the group were smokers.

The volunteers were randomized into one of four groups: placebo alone, placebo plus insulin glargine (Lantus), metformin (an oral anti-diabetes medication) alone, or metformin plus insulin glargine. Study volunteers also received advice on diet and weight.

Overall, the volunteers lost an average of 3.2 pounds during the 14-week study, except for the insulin and placebo group.

As for markers of inflammation, the researchers found reductions in inflammation (as measured through levels of C-reactive protein, IL-6, and tumor necrosis factor receptor 2) for all of the groups. The insulin-plus-placebo group, however, had the smallest reduction in inflammatory markers. For example, C-reactive protein levels went down in the placebo group by 19 percent, in the metformin group by 16 percent and the metformin and insulin group by 20 percent. However, the insulin plus placebo group went down just 3 percent.

Effect of Weight Loss Accounted For

Dr. Pradhan says the researchers adjusted the data to account for the weight loss, and still found a similar effect. She said it may be that the weight changes affected the distribution of fat, and that abdominal fat tends to have more of an effect on inflammation.

"While these two agents didn't lower inflammation [any more than the placebo], they did lower glucose levels and are excellent drugs for preventing microvascular outcomes, like eye and kidney diseases," Dr. Pradhan says. The findings also confirm that diet and exercise can affect inflammation levels, she adds.

"While this is a well-conducted study, there are no big surprises here," says Dr. Vivian Fonseca, chief of endocrinology at Scott & White Clinic in Temple, Tex., and Texas A&M Health Sciences Center, College Station. "There are many drugs that benefit people and reduce cardiovascular risk without decreasing inflammation, and there are drugs that reduce inflammation that have sometimes killed people from cardiovascular disease."

"We're trying to look at this problem the other way," says Dr. Fonseca. She and other researchers across the country will test an anti-inflammatory medication, salsalate, to see if lowering inflammation directly can have an impact on blood glucose levels.

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The link between diabetes and heart disease:

Heart and vascular disease often go hand-in-hand with diabetes. Persons with diabetes are at a much greater risk for heart attacks, strokes, and high blood pressure. Other vascular problems due to diabetes include poor circulation to the legs and feet. Unfortunately, many cardiovascular problems can go undetected and can start early in life.

Serious cardiovascular disease can begin before the age of 30 in persons with diabetes. The two most common types of diabetes are type 1 and type 2. Type 1 diabetes (also called insulin-dependent diabetes mellitus) is an autoimmune disease in which the body's immune system attacks the cells in the pancreas that produce insulin, resulting in no or a low amount of insulin. Type 2 diabetes (also called non-insulin dependent diabetes mellitus) is the result of the body's inability to make enough, or to properly use, insulin.

According to the American Diabetes Association, damage to the coronary arteries is two to four times more likely in asymptomatic persons with type 1 diabetes than in the general population. Because symptoms may be absent at first, the American Diabetes Association recommends early diagnosis and treatment, and management of risk factors.

Many studies demonstrate that persons with type 2 diabetes are at increased risk for heart disease. In fact, one study found that persons with type 2 diabetes without apparent heart problems ran the same risk for heart disease as persons without diabetes who had already suffered one heart attack.

Persons with diabetes often experience changes in the blood vessels that can lead to cardiovascular disease. In persons with diabetes, the linings of the blood vessels may become thicker, making it more difficult for blood to flow through the vessels. When blood flow is impaired, heart problems or stroke can occur. Blood vessels can also suffer damage elsewhere in the body due to diabetes, leading to eye problems, kidney problems, and poor circulation to the legs and feet.

Even when taking proper care of yourself, heart disease may still occur. When risk factors are eliminated (or reduced) in a person with diabetes, the risk for heart disease may be reduced. Taking care of yourself and controlling your blood sugar can often slow down or prevent the onset of complications. Other preventive treatment measures may include:

See a physician regularly.

Have annual electrocardiograms, or EKGs (a test that records the electrical activity of the heart, shows abnormal rhythms, and detects heart muscle damage), cholesterol and blood pressure check-ups, and pulse measurement in legs and feet.

Pay attention to your symptoms and report them promptly to your physician.